[PDF] 3 CEFTIN Tablets 6 CEFTIN for Oral Suspension

View - Download 3 CEFTIN Tablets 6 CEFTIN for Oral Suspension

Previous PDF

Next PDF

1

2 PRESCRIBING INFORMATION

3

CEFTIN

Tablets

4 (cefuroxime axetil tablets)

5 6

CEFTIN

for Oral Suspension

7 (cefuroxime axetil powder for oral suspension)

8

9 To reduce the development of drug-resistant bacteria and maintain the effectiveness of

10 CEFTIN and other antibacterial drugs, CEFTIN should be used only to treat or prevent infections

11 that are proven or strongly suspected to be caused by bacteria.

12 DESCRIPTION

13 CEFTIN Tablets and CEFTIN for Oral Suspension contain cefuroxime as cefuroxime axetil.

14 CEFTIN is a semisynthetic, broad-spectrum cephalosporin antibiotic for oral administration.

15 Chemically, cefuroxime axetil, the 1-(acetyloxy) ethyl ester of cefuroxime, is (RS)-1

16 hydroxyethyl (6R,7R)-7-[2-(2-furyl)glyoxyl-amido]-3-(hydroxymethyl)-8-oxo-5-thia-1

17 azabicyclo[4.2.0]-oct-2-ene-2-carboxylate, 7

2

Z)-(O-methyl-oxime), 1-acetate 3-carbamate. Its

18 molecular formula is C

20 H 22
N 4 O 10

S, and it has a molecular weight of 510.48.

19 Cefuroxime axetil is in the amorphous form and has the following structural formula:

20 21

22 CEFTIN Tablets are film-coated and contain the equivalent of 250 or 500 mg of cefuroxime

23 as cefuroxime axetil. CEFTIN Tablets contain the inactive ingredients colloidal silicon dioxide,

24 croscarmellose sodium, hydrogenated vegetable oil, hypromellose, methylparaben,

25 microcrystalline cellulose, propylene glycol, propylparaben, sodium benzoate, sodium lauryl

26 sulfate, and titanium dioxide.

27 CEFTIN for Oral Suspension, when reconstituted with water, provides the equivalent of

28 125 mg or 250 mg of cefuroxime (as cefuroxime axetil) per 5 mL of suspension. CEFTIN for

29 Oral Suspension contains the inactive ingredients acesulfame potassium, aspartame, povidone

30 K30, stearic acid, sucrose, tutti-frutti flavoring, and xanthan gum.

31
1

Reference ID: 3630885

32 CLINICAL PHARMACOLOGY

33 Absorption and Metabolism: After oral administration, cefuroxime axetil is absorbed from

34 the gastrointestinal tract and rapidly hydrolyzed by nonspecific esterases in the intestinal mucosa

35 and blood to cefuroxime. Cefuroxime is subsequently distributed throughout the extracellular

36 fluids. The axetil moiety is metabolized to acetaldehyde and acetic acid.

37 Pharmacokinetics: Approximately 50% of serum cefuroxime is bound to protein. Serum

38 pharmacokinetic parameters for CEFTIN Tablets and CEFTIN for Oral Suspension are shown in

39 Tables 1 and 2.

40

41 Table 1. Postprandial Pharmacokinetics of Cefuroxime Administered as CEFTIN Tablets

42 to Adults

a Dose b (Cefuroxime

Equivalent) Peak Plasma

Concentration

(mcg/mL) Time of Peak

Plasma

Concentration

(hr) Mean

Elimination

Half-life (hr) AUC

(mcghr/mL)

125 mg

250 mg

500 mg

1,000 mg 2.1 4.1

7.0

13.6 2.2

2.5 3.0

2.5 1.2 1.2

1.2

1.3 6.7

12.9 27.4
50.0
43
a

Mean values of 12 healthy adult volunteers.

44
b

Drug administered immediately after a meal.

45

46 Table 2. Postprandial Pharmacokinetics of Cefuroxime Administered as CEFTIN for Oral

47 Suspension to Pediatric Patients

a Dose b (Cefuroxime

Equivalent)

n Peak Plasma

Concentration

(mcg/mL) Time of Peak

Plasma

Concentration

(hr) Mean

Elimination

Half-life

(hr) AUC (mcghr/mL)

10 mg/kg

15 mg/kg

20 mg/kg 8

12

8 3.3 5.1 7.0 3.6 2.7 3.1 1.4 1.9 1.9 12.4 22.5 32.8

48
a

Mean age = 23 months.

49
b

Drug administered with milk or milk products.

50

51 Comparative Pharmacokinetic Properties: A 250 mg/5 mL-dose of CEFTIN Suspension

52 is bioequivalent to 2 times 125 mg/5 mL-dose of CEFTIN Suspension when administered with

53 food (see Table 3). CEFTIN for Oral Suspension was not bioequivalent to CEFTIN Tablets

54 when tested in healthy adults. The tablet and powder for oral suspension formulations are

55 NOT substitutable on a milligram-per-milligram basis. The area under the curve for the

56 suspension averaged 91% of that for the tablet, and the peak plasma concentration for the

2

Reference ID: 3630885

57 suspension averaged 71% of the peak plasma concentration of the tablets. Therefore, the safety

58 and effectiveness of both the tablet and oral suspension formulations had to be established in

59 separate clinical trials.

60

61 Table 3. Pharmacokinetics of Cefuroxime Administered as 250 mg/5 mL or 2 x 125 mg/5

62 mL CEFTIN for Oral Suspension to Adults

a

With Food

Dose (Cefuroxime

Equivalent) Peak Plasma

Concentration

(mcg/mL) Time of Peak

Plasma

Concentration

(hr) Mean

Elimination

Half-life (hr) AUC

(mcghr/mL)

250 mg/5 mL

2 x 125 mg/5 mL 2.23

2.37 3

3 1.40

1.44 8.92 9.75

63
a

Mean values of 18 healthy adult volunteers.

64

65 Food Effect on Pharmacokinetics: Absorption of the tablet is greater when taken after food

66 (absolute bioavailability of CEFTIN Tablets increases from 37% to 52%). Despite this difference

67 in absorption, the clinical and bacteriologic responses of patients were independent of food

68 intake at the time of tablet administration in 2 studies where this was assessed.

69 All pharmacokinetic and clinical effectiveness and safety studies in pediatric patients using

70 the suspension formulation were conducted in the fed state. No data are available on the

71 absorption kinetics of the suspension formulation when administered to fasted pediatric patients.

72 Renal Excretion: Cefuroxime is excreted unchanged in the urine; in adults, approximately

73 50% of the administered dose is recovered in the urine within 12 hours. The pharmacokinetics of

74 cefuroxime in the urine of pediatric patients have not been studied at this time. Until further data

75 are available, the renal pharmacokinetic properties of cefuroxime axetil established in adults

76 should not be extrapolated to pediatric patients.

77 In a study of 28 adults with normal and markedly impaired renal function, the elimination

78 half-life of cefuroxime was prolonged in relation to severity of renal impairment. In a study of 16

79 adult hemodialysis patients with end-stage renal disease, the majority of a cefuroxime dose was

80 removed by hemodialysis. In a study of 20 elderly patients (mean age = 83.9 years) having a

81 mean creatinine clearance of 34.9 mL/min, the mean serum elimination half-life was 3.5 hours.

82 Despite the lower elimination of cefuroxime in geriatric patients, dosage adjustment based on

83 age is not necessary (see PRECAUTIONS: Geriatric Use).

84 Microbiology: Mechanism of Action: Cefuroxime axetil is a bactericidal agent that acts by

85 inhibition of bacterial cell wall synthesis. Cefuroxime axetil has activity in the presence of some

86 beta-lactamases, both penicillinases and cephalosporinases, of Gram-negative and Gram-positive

87 bacteria.

88 Mechanism of Resistance: Resistance to cefuroxime axetil is primarily through

89 hydrolysis by beta-lactamase, alteration of penicillin-binding proteins (PBPs), decreased

90 permeability and the presence of bacterial efflux pumps.

3

Reference ID: 3630885

91 Susceptibility to cefuroxime axetil will vary with geography and time; local susceptibility data

92 should be consulted, if available. Cefuroxime axetil has been shown to be active against most

93 isolates of the following bacteria, both in vitro and in clinical infections as described in the

94 Indications and Usage section:

95 Gram-positive bacteria

96 Staphylococcus aureus (methicillin-susceptible isolates only)

97 Streptococcus pneumoniae

98 Streptococcus pyogenes

99 Gram-negative bacteria

100

Escherichia coli

a

101 Klebsiella pneumoniae

a

102 Haemophilus influenzae

b

103 Haemophilus parainfluenzae

104 Moraxella catarrhalis

105 Neisseria gonorrhoeae

106
a Most extended spectrum beta-lactamase (ESBL)-producing and carbapenemase-producing

107 isolates are resistant to cefuroxime axetil.

108
b Beta-lactamase-negative, ampicillin resistant (BLNAR) isolates of H. influenzae must be

109 considered resistant to cefuroxime axetil.

110 Spirochetes

111 Borrelia burgdorferi

112 The following in vitro data are available, but their clinical significance is unknown. At

113 least 90 percent of the following microorganisms exhibit an in vitro minimum inhibitory

114 concentration (MIC) less than or equal to the susceptible breakpoint for cefuroxime axetil.

115 However, the efficacy of cefuroxime axetil in treating clinical infections due to these

116 microorganisms has not been established in adequate and well-controlled clinical trials.

117 Gram-positive bacteria

118 Staphylococcus epidermidis (methicillin-susceptible isolates only)

119 Staphylococcus saprophyticus (methicillin-susceptible isolates only)

120 Streptococcus agalactiae

121 Gram-negative bacteria

122 Morganella morganii

123 Proteus inconstans

124 Proteus mirabilis

125 Providencia rettgeri

126 Anaerobic bacteria

127 Peptococcus niger

128 Susceptibility Test Methods: When available, the clinical microbiology laboratory should

129 provide the results of in vitro susceptibility test results for antimicrobial drug products used in

130 resident hospitals to the physician as periodic reports that describe the susceptibility profile of

4

Reference ID: 3630885

131 nosocomial and community-acquired pathogens. These reports should aid the physician in

132 selecting an antibacterial drug product for treatment.

133 Dilution Techniques: Quantitative methods are used to determine antimicrobial minimal

134 inhibitory concentrations (MICs). These MICs provide reproducible estimates of the

135 susceptibility of bacteria to antimicrobial compounds. The MICs should be determined using a

136 standardized test method (broth or agar)

1,2 . The MIC values should be interpreted according to

137 criteria provided in Table 4

2,3

138 Diffusion Techniques: Quantitative methods that require measurement of zone diameters

139 also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds.

140 The zone size provides an estimate of the susceptibility of bacteria to antimicrobial compounds.

141 The zone size should be determined using a standardized test method

4 . This procedure uses

142 paper disks impregnated with 30 mcg cefuroxime axetil to test the susceptibility of

143 microorganisms to cefuroxime axetil. The disk diffusion interpretive criteria are provided in

144 Table 4

3 145

146 Table 4. Susceptibility Test Interpretive Criteria for Cefuroxime Axetil

Pathogen Minimum Inhibitory Concentrations

(mcg/mL) Disk Diffusion Zone Diameters (mm) (S)

Susceptible (I)

Intermediate (R)

Resistant (S)

Susceptible (I)

Intermediate (R)

Resistant

Enterobacteriaceae

a

4 8 - 16 32 23 15 - 22 14

Haemophilus spp.

a,b

4 8 16 20 17 - 19 16

Moraxella

catarrhalis a

4 8 16 ---

Streptococcus

pneumoniae 1

2 4 ---

147
a For Enterobacteriaceae, Haemophilus spp, and Moraxella catarrhalis, susceptibility interpretive

148 criteria are based on a dose of 500 mg every 12 hours in patients with normal renal function.

b

149 Haemophilus spp. includes only isolates of H. influenzae and H. parainfluenzae.

150

151 Susceptibility of staphylococci to cefuroxime axetil may be deduced from testing only

152 penicillin and either cefoxitin or oxacillin.

153 Susceptibility of Streptococcus pyogenes may be deduced from testing penicillin.

154 A report of Susceptible indicates that the antimicrobial is likely to inhibit growth of the

155 pathogen if the antimicrobial compound reaches the concentration at the infection site necessary

156 to inhibit growth of the pathogen. A report of Intermediate indicates that the result should be

157 considered equivocal, and if the microorganism is not fully susceptible to alternative, clinically

158 feasible drugs, the test should be repeated. This category implies possible clinical applicability in

159 body sites where the drug is physiologically concentrated or in situations where a high dosage of

5

Reference ID: 3630885

160 drug can be used. This category also provides a buffer zone that prevents small uncontrolled

161 technical factors from causing major discrepancies in interpretation. A report of Resistant

162 indicates that the antimicrobial is not likely to inhibit growth of the pathogen if the antimicrobial

163 compound reaches the concentrations usually achievable at the infection site; other therapy

164 should be selected.

165 Quality Control: Standardized susceptibility test procedures require the use of laboratory

166 controls to monitor and ensure the accuracy and precision of supplies and reagents used in the

167 assay, and the techniques of the individual performing the test

1,2,4 . The QC ranges for MIC and

168 disk diffusion testing using the 30 mcg disk are provided in Table 5

3 169

170 Table 5. Acceptable Quality Control (QC) Ranges for Cefuroxime Axetil

QC Strain

Minimum

Inhibitory

Concentrations

(mcg/mL) Disk Diffusion

Zone Diameters

(mm)

Escherichia coli ATCC 25922 2 - 8 20 - 26

Staphylococcus aureus ATCC 25923 -27 - 35

Staphylococcus aureus ATCC 29213 0.5 - 2 -

Streptococcus pneumoniae ATCC

49619 0.25 - 1 -

Haemophilus influenzae ATCC 49766 0.25 - 1 28 - 36

Neisseria gonorrhoeae ATCC 49226 0.25 - 1 33 - 41

171

172 INDICATIONS AND USAGE

173 NOTE: CEFTIN TABLETS AND CEFTIN FOR ORAL SUSPENSION ARE NOT

174 BIOEQUIVALENT AND ARE NOT SUBSTITUTABLE ON A

175 MILLIGRAM-PER-MILLIGRAM BASIS (SEE CLINICAL PHARMACOLOGY).

176 CEFTIN Tablets: CEFTIN Tablets are indicated for the treatment of patients with mild to

177 moderate infections caused by susceptible strains of the designated microorganisms in the

178 conditions listed below:

quotesdbs_dbs20.pdfusesText_26

[PDF] ceftriaxone 2g iv administration

[PDF] ceftriaxone brand name

[PDF] ceftriaxone contraindications

[PDF] ceftriaxone coverage

[PDF] ceftriaxone davis pdf

[PDF] ceftriaxone dosage

[PDF] ceftriaxone drug class

[PDF] ceftriaxone generation

[PDF] ceftriaxone indications

[PDF] ceftriaxone interactions

[PDF] ceftriaxone iv

[PDF] ceftriaxone iv administration

[PDF] ceftriaxone oral

[PDF] ceftriaxone sodium

[PDF] ceftriaxone uses